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Breast Cancer in Men

Different biological characteristics and outcomes than in women

First results of the EORTC10085/TBCRC/BIG/NABCG International Male Breast Cancer Program, the largest series of male breast cancer cases ever studied, showed that there was significant improvement in overall survival for male breast cancer patients over the duration of the study, but the improvement was not as good as has been seen for female breast cancer, according to research presented at the 2014 San Antonio Breast Cancer Symposium, held 9-13 December 2014. The study provides information about the clinical and biological characteristics of male breast cancer.

Dr Fatima Cardoso, director of the breast unit at the Champalimaud Cancer Center in Lisbon, Portugal said that male breast cancer accounts for just 1% of breast cancers. In addition, of all cancers diagnosed in males, breast cancer accounts for less than 1%. “Our results provide new insight into the clinical and biological characteristics of breast cancer in men, and show that they are not the same as those previously reported for breast cancer in women,” continued Dr Cardoso.

Male breast cancer is not well understood, and the best way of treatment is not yet known. Currently, treatment strategies for men afflicted with this disease are based on those that have been used successfully for women, and research on the differences between men and women regarding the characteristics of this disease was sorely needed. Only case-control and retrospective studies with small numbers of male patients with breast cancer had been performed, and previous to this study there were no available data from randomised clinical trials, a consequence of the closing of all clinical trials for this patient population due to poor accrual.

Fortunately, the collaborative research strategy whereby the European Organisation for Research and Treatment (EORTC), Translational Breast Cancer Research Consortium (TBCRC), Breast International Group (BIG), and the North American Breast Cancer Groups (NABCG) have joined forces to launch this International Program on Male Breast Cancer, has provided a practical approach to learn more about this disease.

The results tend to show that men diagnosed with breast cancer are not well managed in the clinic. For example, even though most male breast cancers are ER-positive, the study investigators found that only 77% of patients received endocrine therapy, like tamoxifen. They also found that even though 56% of male breast cancers are diagnosed when the tumours are very small, only 4% of patients had breast-conserving surgery; most had a mastectomy, a treatment decision that significantly impacted their quality of life, self-esteem and sexuality.

Analyses of tumour samples conducted as part of this study showed that 99% of male breast cancers were ER-positive, 7% were HER2-positive, and 1% were triple negative and consequently do not respond to hormonal therapy nor anti-HER2 therapies. For women, on the other hand, roughly 70% of breast cancers are ER-positive, 20% are HER2-positive, and 10 to 15% are triple-negative.

Additional findings were that grade 2 invasive ductal carcinomas were the most common histological type, and male breast cancers are usually androgen receptor positive, and of luminal A- like subtype.

Overall, adjuvant radiotherapy appears to have been delivered properly in men with breast cancer, and anthracyclines were preferred as adjuvant chemotherapy and tamoxifen for hormonal therapy following loco-regional treatment.

Three parts of the programme

Dr Cardoso is part of a global network of researchers that includes investigators from all the major breast cancer consortia in Europe and North America. The first goal of the Male Breast Cancer International Program was to analyze the largest series of male breast cancer cases ever studied. The investigators enrolled in the study 1,822 men with breast cancer treated between 1990 and 2010 at 23 centers in nine countries. Clinical data for the patients were analyzed at the EORTC headquarter and tumour samples were analyzed in the laboratories of Edinburgh University, United Kingdom, Erasmus Medical Center in Rotterdam, the Netherlands, and the Fred Hutchinson Cancer Research Center in Seattle, USA. According to Dr Cardoso, it was very important that the tumour samples be analyzed in central locations using the same protocols so that variation in analyses could be minimised.

“We are continuing to analyze the tumor samples that we collected during this first part of the project,” said Dr Cardoso in accompanied press release. “But we have also begun part two, which is the prospective register of all men diagnosed with breast cancer in many European, Latin American, and North American countries during a two-year period. This will allow the collection of a current series of these patients and assert the ability of the network to run clinical trials in this rare disease. We also hope to soon begin part three of the project, which will be a clinical trial to test a potential new treatment option for men with breast cancer.”

The second part of this male breast cancer programme is now open: a prospective international registry of all male breast cancer patients treated at the participating institutions for a period of 30 months with collection of clinical data. Here, the number of patients who could be feasibly recruited for a future clinical trial will be evaluated, patterns of care will be described, and prospective sample collection will be performed in selected countries. A Quality of Life sub-study is also ongoing, using the EORTC QLQ-30 questionnaire and items from the BR-23 and PR-25 questionnaires.

Discussions are already ongoing, for the opening of a prospective randomised clinical trial, as the first project of the third part of the International Male Breast Cancer Program.

Dr Sharon Giordano, chair of the Department of Health Services Research at The University of Texas MD Anderson Cancer Center in Houston, USA is the co-principal investigator of the study with Dr Cardoso.

Funding for this academic study was provided by the Breast Cancer Research Foundation, the EORTC Breast Cancer Group, the Dutch Pink Ribbon, the EBCC Council, the Swedish Breast Cancer Association, and the Susan G. Komen For the Cure.